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Diarylidenecyclopentanone derivatives as potent anti-inflammatory and anticancer agents

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Abstract

Cancer is often associated with chronic inflammation. In order to develop potential anticancer and anti-inflammatory agents a series of 26 diarylidenecyclopentanones (DACPs) Ia–Iv, II, III, and IV were synthesized. Five of the synthesized DACPs are novel (Ih, Ij, Ik, Is, and Iv), derivative Iv was characterized using single-crystal X-ray diffraction study. All the synthesized derivatives were tested for their anti-inflammatory as well as cytotoxicity properties. Compound Is is found to have the highest anti-inflammatory activity (93.67%) by inhibiting PGE2 (prostaglandin E2) production. Three of the DACPs (Io, It, and Iu) were observed to have high cytotoxicity with IC50 value of 8.73 ± 0.06 µM (Io), 12.55 ± 0.31 µM (It), and 11.47 ± 0.15 µM (Iu) against HeLa cells. Further staining and cell cycle analysis was done using these three DACPs to understand their mechanism of action. The G0/G1 phase was observed to be the longest one through which the cells undergo apoptosis.

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Abbreviations

AO:

Acridine orange

COX:

cyclooxygenase

DACP:

Diarylidenecyclopenatnone

DMEM:

Dulbecco's Modified Eagle Medium

ETBR:

Ethidium bromide

mPGES-1:

membrane-associated PGE synthase-1

MTT:

3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide

NCCS:

National Centre for Cell Science

NCI:

National Cancer Institute

PBS:

phosphate buffered saline

PGE2:

Prostaglandin E2

PI:

Propidium Iodide

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Acknowledgements

Authors dedicate the work to Founder Chancellor Bhagawan Sri Sathya Sai Baba. The authors thank CRIF, SSSIHL for providing the characterization facilities. We also thank Sri Swayamsiddha Kar and Dr. Sai Manohar Chelli for their valuable inputs. Nitesh Tamang thanks MOTA for the NFST fellowship (201819-NFST-WES-02502) and Mayank Joshi thanks DST for Inspire fellowship (IF160793).

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Authors and Affiliations

  1. Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, India

    Nitesh Tamang, Siva Kumar B. & Nageswara Rao Golakoti

  2. Department of Biotechnology, Indian Institute of Technology, Chennai, Tamil Nadu, India

    Gayathri Ramamoorthy & Mukesh Doble

  3. Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Punjab, India

    Mayank Joshi & Angshuman Roy Choudury

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  1. Nitesh Tamang
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Correspondence to Nageswara Rao Golakoti or Mukesh Doble.

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These authors contributed equally: Nitesh Tamang, Gayathri Ramamoorthy

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Tamang, N., Ramamoorthy, G., Joshi, M. et al. Diarylidenecyclopentanone derivatives as potent anti-inflammatory and anticancer agents. Med Chem Res 29, 1579–1589 (2020). https://doi.org/10.1007/s00044-020-02578-5

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